The major goal of this research training program is to train the future leaders of medical genetics who will emerge from a variety of training pathways. Many will have M.D. degrees, others will be M.D.-Ph.D.s. For this training grant, we concentrate on the former two groups. M.D.s and M.D.-Ph.D.s with clinical training in Pediatrics, Medicine, Ob.-Gyn., Psychiatry, Pathology and other specialty areas will be eligible for support from this training grant. Combined pediatrics-genetics residents will also be eligible during their 4th and 5th years of residency. The overall training program for these individuals consists of one clinical year during which the fellow has a substantial clinical load and fulfills a portion of her/his didactic course work in human genetics and molecular biology. This first year is funded by the University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia (CHOP), while funds for the research years of the overall training program are sought from this training grant. During the second year, the M.D. fellow completes didactic course work and begins research training. During most of the second year and all of the third and often fourth years, the fellow devotes essentially 100% effort to research in a basic science laboratory. Research opportunities are extremely diverse with training in the laboratories of 47 faculty from 15 different departments at Penn. During the research years, the trainee also takes seminar courses, attends journal clubs, research meetings, and departmental research retreats, and carries out minimal clinical activities, not to exceed 5% effort. Training stipends for these two to three years are requested in this application. The M.D. trainee will likely require further research training (not covered by this training grant), which might be another postdoctoral research experience or a protected faculty appointment with considerable mentoring from a senior faculty member. This grant will fund up to three research years of the M.D. investigator in medical genetics and two years for M.D.-Ph.D. fellows.